Familial hypertrophic cardiomyopathy is caused by mutations in sarcomere protein genes--cardiac troponin T, beta cardiac myosin heavy chain, tx- tropomyosin, cardiac myosin binding protein C, essential myosin light chain and regulatory myosin light chain. However, we do not know if mutations in all of these different genes cause this condition by the same, or different mechanisms. To address this and other related questions we will create murine models of FHC by introducing known FHC- causing mutations into the mouse genome and comparing the effects of these different mutations on cardiac development and function. Because cardiac hypertrophy is a relatively common disease, the results of these studies should be of considerable importance to clinicians and patients as well as to basic researchers. Here we propose the following steps to create the necessary murine models of FHC and to determine the effects of these mutations: a) Create heterozygous and homozygous mice bearing an FHC-causing mutation in their cardiac troponin T gene, alpha tropomyosin gene, or cardiac myosin binding protein C. b) To define the myocardial changes that occur in the hearts of mutant mice bearing an FHC-causing mutations. c) To identify genetic and environmental factors that influence the pathophysiology exhibited by these murine FHC models. d) To assess changes in the beta-adrenergic signal transduction pathways and other biochemical processes of genetically altered myocardium.